The Experts below are selected from a list of 474 Experts worldwide ranked by ideXlab platform
Thomas P Loughran - One of the best experts on this subject based on the ideXlab platform.
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somatic stat3 mutations in Felty Syndrome an implication for a common pathogenesis with large granular lymphocyte leukemia
Haematologica, 2017Co-Authors: Paula Savola, Thomas P Loughran, Markku Kauppi, Oscar Bruck, Thomas Olson, Tiina Kelkka, Soili Kytola, T Sokkaisler, Panu E Kovanen, Marjatta LeirisalorepoAbstract:Felty Syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty Syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. We now aimed to study whether these mutations can also be detected in Felty Syndrome, which would imply for a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty Syndrome patients who were monitored at the rheumatology outpatient clinic for Felty Syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty Syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3 which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that 10 of the 92 assayed cytokines were elevated both in Felty Syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty Syndrome as in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, unified re-classification of these two Syndromes is warranted.
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Somatic STAT3 mutations in Felty Syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia.
Haematologica, 2017Co-Authors: Paula Savola, Thomas P Loughran, Markku Kauppi, Oscar Bruck, Tiina Kelkka, Soili Kytola, Panu E Kovanen, Thomas J. Olson, Tuulikki Sokka-isler, Marjatta Leirisalo-repoAbstract:Felty Syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty Syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30–40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty Syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty Syndrome patients who were monitored at the rheumatology outpatient clinic for Felty Syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty Syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3, which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that ten of the 92 assayed cytokines were elevated both in Felty Syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty Syndrome as they are in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, a unified reclassification of these two Syndromes is warranted.
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pathogenesis of neutropenia in large granular lymphocyte leukemia and Felty Syndrome
Blood Reviews, 2006Co-Authors: Eric Burks, Thomas P LoughranAbstract:T-cell large granular lymphocyte leukemia (TLGL) is an atypical chronic lymphoproliferative disorder derived from cytotoxic T-cells (CTL). Unlike most forms of leukemia, the pattern of bone marrow infiltration in TLGL may be subtle and the cytopenias are often lineage specific, with neutropenia dominating. Both granulocytic survival and proliferation defects are observed and are mediated by humoral and cell-mediated mechanisms respectively. Splenic production of immune complexes induces a neutrophil survival defect, where as Fas expression by leukemic CTL results in a marrow based proliferation defect. These humoral and cell-mediated pathways induce granulocytic apoptosis through independent intracellular mechanisms which are not mutually exclusive and may be observed concurrently in individual patients with either TLGL or FS. A variety of therapeutic interventions have been utilized in the management of TLGL and Felty Syndrome, including methotrexate, cyclosporine A, cyclophosphamide, glucocorticoids, myeloid colony stimulating factors and splenectomy. Their efficacy and mechanisms of action are reviewed.
Paula Savola - One of the best experts on this subject based on the ideXlab platform.
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somatic stat3 mutations in Felty Syndrome an implication for a common pathogenesis with large granular lymphocyte leukemia
Haematologica, 2017Co-Authors: Paula Savola, Thomas P Loughran, Markku Kauppi, Oscar Bruck, Thomas Olson, Tiina Kelkka, Soili Kytola, T Sokkaisler, Panu E Kovanen, Marjatta LeirisalorepoAbstract:Felty Syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty Syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. We now aimed to study whether these mutations can also be detected in Felty Syndrome, which would imply for a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty Syndrome patients who were monitored at the rheumatology outpatient clinic for Felty Syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty Syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3 which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that 10 of the 92 assayed cytokines were elevated both in Felty Syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty Syndrome as in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, unified re-classification of these two Syndromes is warranted.
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Somatic STAT3 mutations in Felty Syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia.
Haematologica, 2017Co-Authors: Paula Savola, Thomas P Loughran, Markku Kauppi, Oscar Bruck, Tiina Kelkka, Soili Kytola, Panu E Kovanen, Thomas J. Olson, Tuulikki Sokka-isler, Marjatta Leirisalo-repoAbstract:Felty Syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty Syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30–40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty Syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty Syndrome patients who were monitored at the rheumatology outpatient clinic for Felty Syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty Syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3, which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that ten of the 92 assayed cytokines were elevated both in Felty Syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty Syndrome as they are in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, a unified reclassification of these two Syndromes is warranted.
Marjatta Leirisalorepo - One of the best experts on this subject based on the ideXlab platform.
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somatic stat3 mutations in Felty Syndrome an implication for a common pathogenesis with large granular lymphocyte leukemia
Haematologica, 2017Co-Authors: Paula Savola, Thomas P Loughran, Markku Kauppi, Oscar Bruck, Thomas Olson, Tiina Kelkka, Soili Kytola, T Sokkaisler, Panu E Kovanen, Marjatta LeirisalorepoAbstract:Felty Syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty Syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. We now aimed to study whether these mutations can also be detected in Felty Syndrome, which would imply for a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty Syndrome patients who were monitored at the rheumatology outpatient clinic for Felty Syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty Syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3 which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that 10 of the 92 assayed cytokines were elevated both in Felty Syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty Syndrome as in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, unified re-classification of these two Syndromes is warranted.
Marjatta Leirisalo-repo - One of the best experts on this subject based on the ideXlab platform.
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Somatic STAT3 mutations in Felty Syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia.
Haematologica, 2017Co-Authors: Paula Savola, Thomas P Loughran, Markku Kauppi, Oscar Bruck, Tiina Kelkka, Soili Kytola, Panu E Kovanen, Thomas J. Olson, Tuulikki Sokka-isler, Marjatta Leirisalo-repoAbstract:Felty Syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty Syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30–40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty Syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty Syndrome patients who were monitored at the rheumatology outpatient clinic for Felty Syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty Syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3, which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that ten of the 92 assayed cytokines were elevated both in Felty Syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty Syndrome as they are in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, a unified reclassification of these two Syndromes is warranted.
Markku Kauppi - One of the best experts on this subject based on the ideXlab platform.
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somatic stat3 mutations in Felty Syndrome an implication for a common pathogenesis with large granular lymphocyte leukemia
Haematologica, 2017Co-Authors: Paula Savola, Thomas P Loughran, Markku Kauppi, Oscar Bruck, Thomas Olson, Tiina Kelkka, Soili Kytola, T Sokkaisler, Panu E Kovanen, Marjatta LeirisalorepoAbstract:Felty Syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty Syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. We now aimed to study whether these mutations can also be detected in Felty Syndrome, which would imply for a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty Syndrome patients who were monitored at the rheumatology outpatient clinic for Felty Syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty Syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3 which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that 10 of the 92 assayed cytokines were elevated both in Felty Syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty Syndrome as in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, unified re-classification of these two Syndromes is warranted.
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Somatic STAT3 mutations in Felty Syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia.
Haematologica, 2017Co-Authors: Paula Savola, Thomas P Loughran, Markku Kauppi, Oscar Bruck, Tiina Kelkka, Soili Kytola, Panu E Kovanen, Thomas J. Olson, Tuulikki Sokka-isler, Marjatta Leirisalo-repoAbstract:Felty Syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty Syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30–40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty Syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty Syndrome patients who were monitored at the rheumatology outpatient clinic for Felty Syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty Syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3, which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that ten of the 92 assayed cytokines were elevated both in Felty Syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty Syndrome as they are in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, a unified reclassification of these two Syndromes is warranted.
